BACKGROUND: New developments in the treatment of lung cancer have necessitated the further histologic and cytologic subtyping of nonsmall cell lung carcinomas. Thyroid transcription factor‐1 (TTF‐1) long has served as the predominant marker for demonstrating lung origin. However, it is also expressed in a variety of other tumors, particularly neuroendocrine neoplasms and, to a much lesser degree, squamous cell carcinoma of the lung. Napsin‐A, which is expressed in lung tissue, is a relatively new marker for lung adenocarcinoma. In this study, the authors examined the utility of napsin‐A compared with TTF‐1 in cytologic specimens of primary and metastatic, poorly differentiated lung adenocarcinomas.METHODS: The archives of the Department of Pathology at The Johns Hopkins Hospital were searched for cytologic cases of poorly differentiated lung adenocarcinoma that were histologically confirmed. In total, 75 patients (cases) along with 95 controls were included, each of whom had adequate cell block material for TTF‐1 and napsin‐A staining. Tissue microarrays of lung adenocarcinoma also were examined.RESULTS: TTF‐1 and napsin‐A were detected in 61 of 75 cases (81.3%) and in 49 of 75 cases (65.3%), respectively. The sensitivity and specificity of TTF‐1 were 81% each; and napsin‐A had a greater specificity of 96%, and sensitivity of 65%. Napsin‐A was not detected in small cell carcinomas or in other carcinomas of nonlung origin except for renal cell carcinoma.CONCLUSIONS: Although TTF‐1 had a higher sensitivity, napsin‐A was useful as a surrogate marker when encountering a poorly differentiated lung adenocarcinoma or an unknown primary tumor, particularly in cytologic specimens and difficult cases. The current results indicate that the dual use of both markers may be necessary to improve diagnostic accuracy. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.

Distinctive histological variants of lung cancer are increasingly recognized to have specific genetic changes that affect tumor biology and response to therapy. In this study, we evaluated true papillary adenocarcinoma of the lung, proposed as a distinct diagnostic category with relatively poor response to therapy, to determine whether these tumors also have specific molecular alterations that would affect sensitivity to chemotherapy. Specifically, we measured protein levels of P53, excision repair cross-complementation 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) by immunohistochemistry and evaluated the Kelch-like erythroid cell-derived protein with cap-n-collar homology (ECH)-associated protein 1 (KEAP1) gene for mutations, correlating mutations of this gene with total and nuclear expression of the nuclear factor erythroid-2-related factor 2 (NRF2). We found high levels of P53 in 23 of the 55 specimens (41.8%), similar to the rate of P53 gene mutations observed in general for pulmonary adenocarcinoma, and levels of ERCC1 and RRM1 also showed distributions similar to those reported generally for non-small lung cell cancer (NSCLC). However, KEAP1 alterations were observed at a significantly higher frequency in papillary adenocarcinoma tumors (60%) than what has been reported previously for NSCLC (3–19%). These mutations of KEAP1 were associated with increased nuclear accumulation of NRF2 in tumors, as expected for functional alterations. Thus, high rates of KEAP1 mutations and NRF2 overexpression in true papillary adenocarcinoma could be related to poor prognosis and chemotherapy resistance. Furthermore, this distinctive molecular characteristic supports the recognition of true papillary adenocarcinoma as a diagnostic entity.

BACKGROUND: Cell block (CB) preparation during the endobronchial ultrasound‐guided transbronchial fine‐needle aspiration (EBUS‐TBNA) procedure plays an important role in the diagnosis of lung cancer and recovery of cellular material for molecular characterization of the tumor. However, the efficiency of the conventional method of CB preparation is suboptimal.METHODS: In the current study, the “tissue coagulum clot” cell block (TCC‐CB) method was used to prepare the CBs and its efficiency was compared with that of the conventional saline rinse cell block (NR‐CB) method. A total of 84 consecutive TCC‐CBs (106 lymph nodes [LNs] and 14 lung lesions) and 28 consecutive cases of NR‐CB (39 LNs and 3 lung lesions) obtained within the same time period were included in the current study.RESULTS: In the TCC‐CB specimens, 94 of 106 LN cases (88.7%) yielded sufficient diagnostic material, as did 11 of 14 lung lesions (78.6%). In the NR‐CB group, which was used as the control, 22 of 39 LN specimens (56.4%) and none of 3 lung specimens (0%) were found to provide sufficient diagnostic material. Although the average size of the LNs in the study group were not significantly different from those in the control group (1.76 cm vs 1.82 cm; P > .05), the overall nondiagnostic rates in the TCC‐CB and NR‐CB groups were 11.2% and 43.6%, respectively (P < .001). The nondiagnostic rates of the lung specimens were 15.4% in the TCC‐CB group and 100% in the NR‐CB group (P < .05). In addition, immunohistochemistry studies and epidermal growth factor receptor (EGFR)/KRAS mutational analyses were performed in 26 and 14 TCC‐CB cases, respectively. With the exception of 1 case, all of them had satisfactory results.CONCLUSIONS: The data from the current study demonstrate that the TCC‐CB method significantly increases the cellular yield of CB preparations without compromising cytomorphological characterization of tumor cells. Cancer (Cancer Cytopathol) 2012;. © 2011 American Cancer Society.